Microbes: From Farm to Fork

15 January 2019
Presented by Chris Smith, Georgia Mills.

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We’re making a meal out of microbes, meet the little helpers that get food onto the table. Plus, in the news, the intelligent material that help wounds to heal, scientists get to the bottom of how norovirus makes us ill, and we explore a mysterious signal from space.

In this episode

Bandaging leg

00:52 - New material helps wounds heal quickly

A chemically intelligent repair material supplies wounds with just what they need.

New material helps wounds heal quickly
with Ben Almquist, Imperial College London

When we injure ourselves, or undergo surgery, tissues have to stitch themselves back together. And as this happens, the chemical environment of the wound, and the types of cells that are present, go through a sequence of changes. And what helps healing at one stage won’t necessarily be the best promoter of repair later on. Instead, what’s needed is a chemically intelligent repair material that can supply just what the repair process requires just when it wants it. And Ben Almquist, at Imperial College London, has developed just such a material that uses parcels wrapped in DNA to dispense healing signals on demand; he explained to Hannah Laeverenz Schlogelhofer how it works.

Ben - So what we want to do is we want to design materials that can interact with our wounds as they heal. So, if you think about something like a bandage, it really just sits there and it doesn't actually interact with our wounds. And so what we want to do is design materials that can change and interact over time with the wound to promote and help wounds heal.

Hannah - How does this work?

Ben-  So we have developed a way for us to design materials that have kind of hidden instructions in them that cells can unveil when they need them. And those instructions can be specific to what those cells need to help heal a wound. So the best way to think about this is to think about getting home and seeing one of those packaging envelopes that has arrived for you and what you do is you take it and you pull on the tab to open it and then remove kind of whatever's inside. Our technology works in a very similar way. So we have these packages that are available within the scaffolding that cells crawl around in, and they can come and pull on them and release these instructions and activate these instructions that tell them what to do.

Hannah - So what are these envelopes made of?

Ben -  These envelopes are made out of DNA. Most people think of DNA with genes and things like that but it can be developed and used as a material because it has very specific interactions. And so we can use it kind of like a programmable material to build with. And so what we do is, by using a single strand, it folds up into a little three dimensional shape, kind of like tying a bow, and this bow then interacts very specifically with a protein of interest. So these proteins can do a variety of different things. Depending on the protein that we target, they could, let's say, promote blood vessels growing or promote cells that build more scaffolding to come into the wound or in the case of something like bone they might promote bone growth and mineralization.

Hannah - And so how do you make sure that this envelope opens at the right moment?

Ben - So one way we can do this is by tuning it to which cells are present in the wound as it heals. So if you think about wound healing when you first have a wound there is one type of cell, let's say from your immune system, that helps kill off bacteria and removes some of the damaged tissue that's there. But then over time the cells that are present change. And so what we can do and what we have shown is that we can design it so that different packages can be opened by different types of cells.

Hannah -  Once the wound heals what happens to the material after that?

Ben - So one of the nice things about this is that it's made out of DNA and inherently our bodies know how to deal with DNA. And so as the wound heals you can have it so that it breaks down in our cells and our bodies know how to get rid of it and recycle it.

Hannah - What are the next steps for this research.

Ben - Currently the next step of this is that we're testing this in the context of broken bones that don't heal. And so we have a model system where we can actually put these in and see whether or not we can heal these defects that normally don't heal. But then going forward this will provide the kind of foundational research that we need to begin exploring transitioning this to the clinic.

There's a lot of benefits of this strategy: it's highly flexible, it's highly programmable and there's a lot of benefits too from being DNA which every year gets cheaper and cheaper to make. And one of the nice things is that it uses this DNA that is already used clinically and so there's a background that's available in terms of - are these safe, are they effective? And so we're hoping that we can leverage that a bit to speed up the transition to the clinic.

Space

05:23 - Mysterious radio signals from space

What are these strange messages, and should we be using the A- Word!?

Mysterious radio signals from space
with Fran Day, University of Cambridge

There have been recent reports of a mysterious repeating radio signal coming from a distant galaxy one and a half billion light years away. What are these strange messages, and should we be using the A- Word!? Astrophysicist Fran Day, from the University of Cambridge, has been looking at the papers describing the phenomenon for Georgia Mills and Chris Smith. Starting with, what exactly is this signal? 

Fran - This is fast radio bursts, which do exactly what they say on the tin. They’re bursts of radio waves, which have been observed all across the sky. They were first discovered in 2007 and we don't know where they come from. So they really are mysterious. The exciting thing about this result is that they've discovered 13 new fast radio bursts and one of them is a repeating fast radio burst.

Georgia - And what does that mean, "repeating"?

Fran - This means that when we look at one point in the sky we see it do a radio burst several times.

Georgia - Right. And is it the same sort of pattern going ahead again and again?

Fran - It’s quite irregular. So they vary on the order of days to months. There'd be like a few in a day and then there was one that was like a month later or something. And there's only been one other repeating fast radio burst ever discovered. All the rest, we see one burst and then we never see anything from that patch of sky again. So this is quite a big clue to their origin that there's now two of these repeaters.

Georgia - Do we have any ideas what might have caused these?

Fran - We don't know is the short answer, but scientists have an awful lot of theories. So among astrophysicists some of the more popular theories are that they might be collisions between black holes or neutron stars. They have an awful lot of energy. A fast radio burst has as much energy in a millisecond as the sun produces in 80 years. So they need to be very energetic objects. They could also be especially energetic supernova, which is the explosion at the end of a star's life. There are also more exotic theories, for example in some theories of dark matter you can get a dark matter induced collapse of a neutron star that would lead to a big radio burst. And of course occasionally people suggest that they're aliens. But I think at the moment there isn’t evidence for this.

Georgia - I knew it. I knew it would be too good to be true. How did we find them?

Fran - They're observed using a radio telescope. So the latest result is from the CHIME Radio Telescope, which stands for the Canada Hydrogen Intensity Mapping Experiment. So this is a new telescope, it just went online in March, and it's already obviously discovered huge results.

Georgia - And is it a matter of being in the right place at the right time or do you think we're going to see more and more of these now?

Fran - I think we'll see more and more. CHIME has a very large field of view, it looks across a lot of the sky at once, and it has very good amplifiers, which makes it very good at searching for fast radio bursts. So now we've got this up and running. I think we’re likely to see more discoveries from CHIME.

Chris - And, Fran, does the fact that you've got one that keeps coming back, does that mean that we can now use that to try and study what these things are because we can look at what is in that patch of space using a range of different techniques to see what else is there and that will then hopefully see what the source of the fast radio repeat burst is?

Fran - Hopefully. We don't know whether the repeaters are the same thing as the isolated fast radio bursts. It might be that they're entirely different objects. But certainly a good next step is to look very carefully at the patches of space where we know we've seen fast radio bursts to see if there are signals in other wavelengths...

Sleeping father and baby

10:08 - Mythconception: Genetic Inheritance

Mitochondrial inheritance has spun the scientific community on its head...

Mythconception: Genetic Inheritance
with Eva Higginbotham, University of Cambridge

Normally when we have a mythconception we debunk a commonly-held but unfortunately-incorrect idea; but this time it’s actually the scientific community that’s had one of their own assumptions overturned. Eva Higginbotham has been unravelling the story behind a special kind of genetic inheritance...

Eva - In almost all your cells there are special structures called mitochondria, and these important little guys make almost all the energy a cell needs to do its job. Kind of like cellular power stations. Mitochondria are also special because they have their own DNA that is completely separate from the rest of the cell. And it's been known for a long time that in almost all animals only the mother passes down her mitochondrial DNA to the next generation. What that means is when an egg and sperm fuse together, the egg actively destroys all of the sperm’s mitochondria leaving only the mother's mitochondria to populate the embryo. So you could say that, really, we get a little more than half of our total DNA from my mother as we get all of our mitochondria from her too. Or so everyone thought.

There's been some new research that has tipped the scientific community’s understanding of mitochondrial inheritance on its head.

A four year old boy who was suffering from fatigue had his mitochondrial DNA sequence examined to see what could be wrong. The doctors were shocked to find that he had not just one population of mitochondria, as you might expect, but two. It was so surprising that they ran the test multiple times in multiple labs to be absolutely certain of what they were seeing: A human with mitochondria from two parents. They started testing the boy's family and with further investigation they discovered that his mum was the originator of this strange phenomenon. She had inherited 60 percent of her mitochondria from her mother and 40 percent from her father.

With this in mind they started looking for other families who might have a similar mixture of mitochondria and found 17 people from three different families across the world. Most of these people were perfectly healthy so it doesn't seem like getting some of your mitochondria from your dad is harmful, in and of itself. The scientists expect that the reason these families are passing down some of dad's mitochondria is probably not a case of “dad's mighty mitochondria” and is more likely due to a defect in the system that would normally destroy the sperm’s mitochondria at fertilisation.

There's been a bit of a debate for the last 20 years or so about whether this kind of mitochondrial inheritance is possible and this new research is really strong evidence that yes, it can definitely happen in some circumstances. And this might open the door for some novel mitochondrial treatments as currently, there are no cures for some of the most devastating mitochondrial disorders.

The other thing is, because we don't test people's mitochondrial DNA unless they seem to be suffering from some kind of mitochondrial disorder, and because it seems like inheriting a mixture of mitochondria doesn't make you sick on its own, it could be that dads are passing down their mitochondria more often than we ever imagined. That said the egg is normally so good at annihilating the sperm’s mitochondria that paternal mitochondrial inheritance is still likely to be incredibly, incredibly rare.

Man gripping stomach

13:25 - Scientists find new way to target norovirus

The pesky virus invades cells and there are unfortunately no vaccines or drug treatments that can stop it... Yet!

Scientists find new way to target norovirus
with David Bhella, University of Glasgow

Now this time of year is notoriously bad for taking people out with various bugs and illnesses. And one of the worst offenders is norovirus. Every year millions of people succumb to norovirus infections, which lead to severe doses of D and V - diarrhoea and vomiting. The infection often also causes explosive outbreaks in schools, care homes and hospitals, and there are unfortunately no vaccines or drug treatments that can stop it yet. But now scientists at the University of Glasgow have discovered how this family of viruses completes a critical step that enables them to infect the cells in our intestines: contact with molecules on the cell surface triggers the virus to change the shape of its outer coat, creating a tube that connects the inside of the virus particle with the inside of the cell, allowing the viral genetic code to invade the cell. Chris Smith spoke with David Bhella from the study.

David - All viruses need to replicate inside ourselves. They can't grow by themselves so they want to gain access to ourselves and then turn the machinery of our cells into factories to produce more viruses. So we set out to understand how this family of viruses which includes norovirus can cross the cell membrane and enter our cells.

Chris - They’re excruciating small though these viruses aren't they.

David - Yes viruses are absolutely tiny. I think the thing I find amazing about viruses is they're actually smaller than the wavelength of light, to give you an idea of scale if you put 50000 viruses in a row, that row would be about the size of the full stop.

Chris - Which of course is a big challenge for you because you're trying to understand how this entity is infecting a cell but you can't see it, or can you? So how have you actually done the study?

David - So we used a technique called cryo-electron microscopy, electron microscopes use electrons which have a much smaller wavelength which allows it to see smaller things basically. Cryo-electron microscopy is a very powerful method, it's really emerged just the last few years as a technique that allows us to understand the shapes of biological molecules at the atomic level. So we can see the structure of the virus in terms of the atoms it is made of. And this gives us very powerful insights into how the virus does what it does.

Chris - So using that technique you can watch what the viruses do as they engage with the cell surface and then smuggle themselves inside. And that's enabled us to understand a bit more about the actual process, the nuts and bolts that are going on, when the virus particle does that.

David - Yes. So we wanted to understand the mechanism the viruses used to gain access to our cells. So for a virus to get into our cells it has to cross this cell membrane. So viruses are very tiny comparatively the cell is huge, and it's surrounded by this membrane which is like a fatty layer that the virus needs to try and cross. And it's like a brick wall. So viruses have evolved to bind onto molecules on the cell surface, we call the receptor. So the virus binds onto a receptor and then it tricks the cell to take the virus inside the cell through a process known as endocytosis and involves bringing things into a bubble or vesicle. So the virus can cross the cell membrane but it's still enwrapped in this vesicle called the endosome and the virus needs to break out of that. And it's a very difficult challenge for the virus to try and break through a membrane. So it's still basically outside the cell. It hasn't entered the cytoplasm of the cell.

Chris - I suppose it's a bit like if I partially inflated a balloon stuck my fingers in I'd end up with a finger inside the balloon but it's still got a layer of balloon around my finger. The problem for the virus is how do I get across that layer of rubber so that I'm really inside the cell. So how how have you attacked this and how do they do it?

David - We looked at the structure of the virus as it engages the receptor. And we did this by taking the virus and coating it in a fragment of the cell receptor that it binds to. And we discovered that it causes a large structural change in the virus. And we found this structural change results in the formation of a tube which likes to insert into membranes. So we think that this tube will provide a channel through which the virus can inject its genes into the cell where it can then begin to take over and turn that cell into a virus making factory.

Chris - So you've got this structure this tiny viral particle and it's basically protein which is its outer coat. And when it comes into contact inside this bubble with the receptor it likes to dock with, this forces that the virus proteins to rearrange themselves and change shape. And one group of them in particular forms this channel and that connects the inside of the virus particle to the inside of the cells so that's the portal through which the genetic information can flow.

David - Exactly right.

Chris - Does this mean then now you understand this a lot more that we know what we might have to go after if we're going to come up with an anti-norovirus drug?

David - What our study does is it provides another target in our attempts to devise methods for preventing norovirus disease. So we now understand the structure of this tube and have a good idea of what the mechanism will be that leads to genome release. So this gives us the insight necessary to try and devise tests that we could use to screen drugs to prevent that process and of course if you can stop the very first step of infection then you're going to stop the spread of virus. And that's a very powerful thing to try and go after.

Termites in ground

18:54 - Termites help rainforest survive drought

Scientists had overlooked the unlikely hero that helps the ecosystem to defend itself.

Termites help rainforest survive drought
with Hannah Griffiths, University of Liverpool

According to the conservation organisation Global Forest Watch, we lose a football-field sized patch of rainforest every second. The land is used for logging, cropping and housing and is also threatened by the effects of climate change. So scientists are working hard to understand how best to conserve the rainforests that we do have. And they discovered recently that we’d previously overlooked an unlikely hero that helps the ecosystem to defend itself in the face of droughts. Izzie Clarke spoke to researcher Hannah Griffiths from the University of Liverpool, to find out what it is...

Hannah - Principally we're interested in quantifying exactly what role termites have in maintaining ecosystem functions in the rainforest, but it just so happened that our large experiments happened to coincide with the big El Nino drought of 2015 and 2016. So we saw this as a really exciting opportunity to not only look at how termites influence ecosystem processes. We can actually look at how these ecosystem processes changed in response to drought and how termites might be responsible for maintaining some of these processes.

Izzie - So what were these termites doing during that massive drought?

Hannah - Yes, one of the really exciting and sort of surprising results was that their abundance our anchor and counter rates of termites almost doubled during the drought and this had a big impact on some of the processes we were measuring. So, firstly soil moisture: we had these experimental plots where we experimentally suppressed the numbers of termites, so we had areas of the forest where there were fewer termites and we had control areas where we haven't affected the communities. We found where termites were present during the drought soil moisture was higher, leaf litter decomposition was also higher,  the heterogeneity (the variability of nutrients in the soil) was also higher. And this led to an increase in seedling survival rates. So where termites represent all of these things increased and where they were absent we saw a decrease in these activities, but only during the drought. These differences between the control and the suppression plots were only evident during the drought.

Izzie - So during a normal time it's sort of quite a balanced level, but during these droughts you'd almost expect the opposite to happen; that during a drought everything gets a bit drier and  more arid.

Hannah - Exactly. That's exactly what we're expecting to see, so I mean of course during the drought everything did dry up. The forest is quite stark. You used to walk in through the forest and the leaf litter is wet and squishy, there's water dripping off the leaves. But during the drought everything just gets crispy and dry, and the trees start losing their leaves because everything's very, very stressed. So we expected all of these processes, this decomposition,  the soil moisture, that too to decrease. We actually found that where termites were present they maintained these processes which was really exciting and really surprising.

Izzie - I see! So they're like these little engineers that help almost extract all of these nutrients which then help the rainforest keep taking over.

Hannah - Yeah that's exactly what we found.

Izzie - Do we know why this happens?

Hannah - We don't know exactly why. We can hypothesize as to why termites might be increasing in abundance during droughts. Termites move around the forest in tunnels largely underneath the soil surface, and it could be that under normal conditions where it's very very wet, it's actually quite difficult for them to move around them, and where the soil is dried out a little bit it could just be that they can simply move around more easily; their tunnels are less waterlogged. It could also be because, perhaps, they'd be released a little bit from predation from things like ants that perhaps don't do so well in the drought. So we don't know exactly why they increase in abundance during droughts but we've got some inklings that need to be tested further.

Izzie - And why is this so important?

Hannah - With climate change we know that drought is going to increase in frequency and severity. That's been predicted. We know that these rainforests are going to be increasingly stressed. We also know that where you disturb rainforest systems; where you selectively log or deforest, termite communities are affected - they're negatively affected. Diversity in the abundance of termites decrease and we know that termites are really important for keeping things going during the drought.

This means that we've got this massive area of sort of human modified forests where termites are reduced. This means that these forests are less resilient to drought, essentially, because of the reduction in the termite communities. And the other thing is, I think, this is sort of on a broader scale not just thinking about termites: I think it's demonstrating yet again the need to conserve intact biological communities because until we've looked at termites during the drought and outside of the drought, we wouldn't have known they were this important until the system was stressed. And that means there could be many other ecosystem processes and many other organisms that carry out these processes we haven't yet measured. But we're continuing to erode biodiversity which means we don't not know what protection we're losing until it's already gone.

Hands holding soil

25:07 - Microbes: Starting in the soil

Soil isn’t just a source of water and minerals for plants; it’s a whole ecosystem teeming with microscopic life.

Microbes: Starting in the soil
with Giles Oldroyd, University of Cambridge

We’re beginning our microbial journey in the soil. Soil isn’t just a source of water and minerals for plants; it’s a whole ecosystem teeming with microscopic life. And some of these microbes form special relationships with plants that enable them to grow in places - and produce yields - they otherwise couldn’t. These include so-called nitrogen-fixing bacteria.

These bacteria can grab nitrogen from the air and turn it into a form that works as a fertiliser. But only some plants have the genes that enable them to team up with these microbes so they can benefit from this effect. So scientists at Cambridge University’s Sainsbury Laboratory are exploring whether they can move the genes from plants like peas, which can do this, into plants like barley that currently can’t so we can reduce the amount of fertiliser these crops need. Hannah Laeverenz Schlogelhofer went armed with a shovel to meet Giles Oldroyd to find out how...

Giles - I'm going to dig up this plant that's just growing. You can see the roots that havegrown down into the soil and this is the interface where the plants are forming these beneficial associations with microorganisms. In this handful of soil there's gonna be billions of bacteria. It's a very very rich environment for microorganisms. There's lots of fungi, lots of bacteria, a lot of them are saprophyds - they’re just living off the decomposition of the soil. But some of those microorganisms are very specialised to associate with plants.

Hannah - Microorganisms can feed plants two essential nutrients. Fungi can provide phosphates and bacteria can provide nitrogen. A special group of bacteria called Rhizobia have the ability to turn nitrogen from the air into ammonia

Giles - Only a few species of plants - the legumes, that’s peas and beans - associate with nitrogen fixing bacteria and the plant roots grow down into the soil. They find the bacteria that are living in the soil and then attract those bacteria into their roots and the bacteria colonise the roots of the plant and then do the nitrogen fixation inside the roots of the plant.

Hannah -  In agriculture, rather than relying on bacteria in the soil, fertilisers are used to provide crops with the nitrogen they need. But fertilisers are used in huge quantities and have major environmental impacts...

Giles -  It washes into our rivers and streams and oceans and seas and causes major problems to biodiversity and aquatic systems. It also results in a lot of nitrogen pollution in the atmosphere. When you spray the soils with these nitrogenous fertilisers some of it is converted to gaseous forms of nitrogen, called nitrous oxide, and they're incredibly potent greenhouse gases. They’re about 35 times more potent as a greenhouse gas than carbon dioxide. Agriculture in total accounts for about 30 percent of greenhouse gas emissions globally and a lot of that is coming from nitrogenous fertiliser application.

If we can reduce that amount of nitrogen fertilisers that are applied then we address the problems with water pollution but we can also address some of the greenhouse gas emissions from agriculture. There's a huge potential here to bring the power of soil microorganisms into agriculture for the acquisition of nitrogen and phosphorus

Hannah - Only legumes can form associations with nitrogen fixing bacteria. However by transferring this ability to other plants, this might change in the future. Specific genes can be isolated and taken out of legume plants, like peas. Once isolated a naturally occurring process called bacterial gene transfer is used to put the genes from legumes into barley.

Giles - We have those engineered barley plants. We're just in the process of working out which plants express those genes well and then we're testing all the effects of having transferred those genes into barley and so in two years time, if you come back to me, I hope I have a much better answer as to what the implications of this engineering is.

Hannah - We then slipped on some lab coats and went to take a look at these genetically engineered barley plants.

Giles - We're now down in the bowels of the Sainsbury lab where we grow all the plants and these are genetically modified plants. We have to do it in a very tightly controlled environment so  there's no escape of seed from any of this environment.

We can go into the growth room now and you can see there is a lot of barley plants growing here. So these are genetically modified plants that are carrying some of these genes from peas that we hope will transfer this nitrogen fixing symbiosis.

Hannah - And they just look like normal barley plants.

Giles - Yup. So that they're very normal barley plants, they behave just like a normal barley plant. They're just carrying a few extra genes from peas that will affect how they associate with the bacteria in the soil.

Hannah - Why is it really noisy in here?

Giles - It’s so noisy simply because we have to control the heat. So we've got a lot of airflow moving in here.

Hannah - Is that what’s spraying in from the ceiling?

Giles - The spraying in is just controlling humidity. We're trying to create the optimal environment for these barley plants to grow by doing so using lights and humidity and air control.

Hannah -  To escape the noise and humidity we headed back to Giles's office. The genetically engineered plants hold huge potential to reduce our reliance on fertilisers and harness the nitrogen fixing abilities of microbes. But when will the crop be ready to grow in the field?

Giles - It is very hard for me to put a timeframe on it because if we're right in our assumptions right now, then it’s actually very few genes, then I would say there's probably a 10 year window but we are working with the unknown. It's the nature of science, there are no guarantees.

Hannah - And like with any new technology potential safety concerns also need to be considered.

Giles - Right now we don't have those crops right. So we don't have the ability to test the safety concerns but it is something that we have to definitely consider. It would be a major trait that you're putting into cereals. And so we'd have to consider the safety implications for both the environment and for human health. But I think that right now the potential of this technology, particularly the potential of the technology to reduce agricultural pollution, is so great that we really have to crack on and do it. Acknowledging that those risks exist and doing what we can to mitigate those risks

Fresh Cabbage

31:35 - From fresh vegetables to fermented food

We can use other microbes to unlock flavours and energy locked up chemically in harvested food.

From fresh vegetables to fermented food
with Ljiljana Fruk, University of Cambridge

Once we’ve grown and harvested crops we can use other microbes to unlock flavours and energy locked up chemically in food. This is the process of fermentation. And here to give us a digestible account of how it works is Cambridge University chemist, Ljiljana Fruk. And she brought Chris Smith some cabbage...

Ljiljana -  I actually did and I did this experiment myself. So we are going to test it and this is a sauerkraut made by Ljiljana. This is the starting reagent.

Chris -   Okay, so sauerkraut is made from cabbage seed, you’re offering me a jar jammed with raw cabbage. I’ll just grab some of that.

Ljiljana - Yes it is.

Chris - You want me to eat this?

Ljiljana - Yeah I want you to try this.

Chris - I quite like cabbage actually. That’s quite nice, actually.

Ljiljana - Yeah but it doesn't taste like much doesn't it? But if I offer you now a fermented cabbage, which we know as a sauerkraut? Tell me if you would like that a little bit more.

Chris - Okay. So what Ljiljana is now giving me is a plastic pot. You can still recognise this as cabbage in here but it's almost translucent. So here we go.

Ljiljana - Yeah. And it's softer. I think you would feel. I think you would admit it has a little bit more flavor.

Chris - It has a lot more flavor. It's a sort of vinegary texture. So a little bit of that and it's much more acid.

Ljiljana - Yes.

Chris - And it's much softer.

Ljiljana - Yes.

Chris - So I can almost melt away the cabbage with my tongue just rubbing it against the roof of my mouth, rather than having to physically masticate it with lots of jaw action

Ljiljana - Absolutely.

Chris - Now you're calling it fermented cabbage. You haven't done anything apart from let microbes do that I presume. This is the work of microorganisms.

Ljiljana - Exactly, some microorganisms which are living in the leaves of this cabbage are actually there and they have done this process. You just have to treat this cabbage with a little bit of salt, so you have to put salt in water, and you have to keep this cabbage in an airtight container. And these microbes which are present on the leaves will make this chemical reaction go faster and produce then, a range of chemicals and products which are not originally present in the cabbage,

Chris - So critically it's the conditions in which you keep the material once you have chopped it up and prepared it. So the lack of air. You've excluded oxygen. And the salt, what does that do? Select for the right sorts of bugs. So the raw cabbage is going to be covered in a whole population of microbes isn’t it?

Ljiljana - Yes, exactly. And in general, you know, the microbes will be in air that will be on our skin so they’re in the plants as well.

So by adding the salt you are selecting for good bacteria that will do some of the fermenting reactions and they will produce acid as a product. And this acid will then select for another type of bacteria which is again good, which will then induce a flavor enhancement of this food. So what is interesting about this is that despite these bacteria being the same in Croatia or in Britain, they will still have a slightly different product just because the cabbage will be a little bit different because it's grown differently. And I think this is the beauty of fermentation particularly for food preservation or for enhancing the quality of food, that you can have the same types of microbes maybe in a little bit of a different ratio and they will give you a slightly different product.

Chris - It's the bacteria liberating various chemicals that they have the biochemical knowhow written into their genes to release, from the food.

Ljiljana - Exactly.

Chris - But you are forcing the direction they take because you make the conditions ideal for just some of them. Because I wanted to touch on the difference between food spoilage and fermentation because if I took that same cabbage with those same colonies of microbes and I just left it on the table, or in the same pot but not under the conditions you put it in.It wouldn't be half as appetising.

Ljiljana - Yes and you probably had that already so you would have this, kind of, gooey black mass which will be formed and this is because you are now having different conditions which will select for negative bacteria, for these bad bacteria that will cause the rotting. So it's a thin line between the fermentation, between the good and the bad. And it's always about the ratio. And the interesting thing is that we have also in our gut the same types of bacteria, similar types. Some of them are good, some of them are bad so it's very important to keep this balance
Chris - You know a little bird told me, Ljiljana, that you're actually going to open a restaurant which is informed by this technology.

Ljiljana - Yes. And we are unfortunately not the first one so there is a restaurant in Copenhagen called Noma, a famous restaurant that started working on fermentations. And so a friend of mine is a chef and we realised that fermentations are extremely important for unlocking the flavours. So we are going to study some original wild organisms, microorganisms and see how they're affecting the food in geographic context. How is the food in Southern Europe different from the Northern Europe? And it will depend on the fermentation conditions.

Chris - Where’s the restaurant?

Ljiljana - In Zagreb. So it's opening in a month.

Chris - Oh no! I love Zagreb. It's a beautiful city. I was there a year or so.

Ljiljana - So you will get an invite but you need to do some work in our fermentation lab as well. So you might have your own strain of microorganisms. The Naked Scientists strain

Chris - And apart from cabbage what else are you going to ferment.

Ljiljana - So we will do vinegars as well, we will do all kinds of sauces and you can basically ferment any kind of vegetables and foods which can be found in that part of Europe.

Cow in a farm

37:22 - Digesting the science of Ruminants

It’s not just us humans that take advantage of fermentation to enhance food. This biochemical process also happens in the stomachs of a group of animals called ruminants, including cows.

Digesting the science of Ruminants
with Chris Creevey, Queen’s University Belfast

It’s not just us humans that take advantage of fermentation to enhance food. This biochemical process also happens in the stomachs of a group of animals called ruminants, including cows. Joining Georgia Mills to spill the guts on the science of cow digestion was Chris Creevey from the Institute for Global Food Security at Queen’s University Belfast. But why are microbes important to cows?

Chris - Mammals in general are not very well equipped to digest the carbohydrates that are found in plant cell walls so ruminants like cows and sheep and goats and giraffes have evolved a multi chambered stomach; the first chamber which is the largest and contains a highly diverse microbial community whose sole job is to digest and break down those carbohydrates into more easily absorbed forms for the host.

Georgia - Right. So the cows have such a poor poor choice of diet, I suppose. If they didn't have this community of microbes inside them, they just wouldn't be able to digest the grass.

Chris - That's exactly it. In reality, the cows are not really living off the grass as much as they are living off the microbes themselves. The activity of the microbes and even down to the cell walls of microbes themselves are quite important as a protein source for the cows.

Georgia - Right. So they're eating the grass to feed the microbes and then the microbes are feeding them.

Chris - Yeah you can look at it that way.

Georgia - Interesting. And what about when the microbes are breaking down all this grass? What what kind of things does that produce?

Chris - In general, it produces a lot of nutrients which are very important to the cow. But there are also... this community is quite diverse: there's bacteria, archaea, fungi. And some of these are not very important to the core fermentative process that's ongoing, some of them are kind of like hanging on on the side and being a bit opportunistic. One of those is the archaea, which are utilizing free hydrogen in the in the room and as part of their metabolism are producing methane as a byproduct.

Georgia - Right. And what is methane and why is this a problem?

Chris - For us, one of the issues about methane is that it's a potent greenhouse gas, It's about 24 times more potent than than carbon dioxide as a greenhouse gas. So when you add up the large numbers of animals that are around the world in agriculture, it adds up to a significant number of potentially greenhouse causing emissions. Up to about 7 or 8 percent of global emissions on average.

Georgia - Right. And I have to say you dispelled me of a notion I had before when we were talking before the show. I always thought cows farted out methane.

Chris - Yeah. This is one which a lot of people have. Because the rumen in is the very first chamber in the digestive system, the methane is burped out. The vast majority of it. So yes, no they don't fart that much methane.

Georgia - Either way, charming. Is there anything we can do about this?

Chris - So there's a lot of research ongoing, looking at different ways of reducing methane and also to increase the efficiency of these animals in general, because the methane production itself represents a loss of energy to the cow. So if you can decrease the methane then you can increase the amount of energy getting into the animal.

These are taking different forms: some of them are additives; some additives into feed such as the algae is a very interesting potential for reducing methane; other ways which may work and which are being investigated are looking at breeding animals, because you may be a to breed them to produce less methane; or maybe even you can inoculate them and give them a vaccine to produce their own antibodies to specifically reduce the archaea in the rumen. So there’s a lot of very interesting research.

Georgia - Could we get some cows to burp our oxygen instead of methane?

Chris - Well that would be quite a feat. The rumen in is a very anaerobic environment, there is no oxygen really in there at all. And the organisms that live there are highly sensitive to it, so any oxygen that is in there can actually stop the whole fermentative process from occurring at all. So perhaps not oxygen.

Georgia - Well never mind. And given that they're so important, what happens when, say, a farmer gives antibiotics to an animal? Could this potentially wipe out this community and mean they’re unable to digest grass?

Chris - In general the antibiotics tend to be quite specific to certain groups of organisms so they don't tend to wipe everything out. Antibiotics have been used traditionally in the past as an additive in feed simply just to increase the growth rate of the animals. That's primarily in feedlot situations. But that practice has been banned here in the EU since the early 2000s and it's being gotten rid of in other jurisdictions around the world - and this is quite important because what we don't want is a situation where we increase the incidence of things like antimicrobial resistance genes, and microbiomes that are associated with with our food chain.

Georgia - Right. So if we pump antibiotics into cows, then antibiotic resistance can sort of grow in them. And then, I guess, we eat the cows?

Chris - Yeah it's complex because, you know, antibiotics are natural compounds produced by microbes and they're found a lot in these communities and these microbiomes. And as such you always find antimicrobial resistance genes as well because it's kind of like a warfare between the two groups.

I guess it's always there, but if we add in antimicrobials to the system what we can do is increase the prevalence of the anti-microbial genes in the community, and we can risk that community becoming a reservoir for antimicrobial resistance genes to be transferred in down the food chain and and even possibly into human pathogens, so we really have to be quite careful about how we use them.

Blocks of cheese

43:00 - Three cheers for cheese... and microbes!

How can two very different cheeses be made from the same milk?!

Three cheers for cheese... and microbes!
with Bronwen Percival, Neal’s Yard Dairy

We've got cows covered! But, apart from methane, what else comes out of a cow? Milk, of course; and what does milk make? Well the answer is one of our favourite treats! Hannah and Adam from the team gave us a quick-fire introduction to how cheese is made, an art that goes back over 7000 years. Plus Chris Smith was joined in the studio with Bronwen Percival; she’s the Cheese Buyer at Neal’s Yard Dairy in London and is also co-author of the book Reinventing the Wheel - Milk, Microbes and the Fight for Real Cheese.

Hannah - The first cheese was probably made by accident.

Adam -  Historians believe that people discovered the cheesey potential of milk thousands of years ago when they were storing milk in the stomach of calves.  After leaving it there for too long the liquid milk started to clump together.

Hannah - Luckily, cheesemaking has come a long way since then. There are now hundreds of different types from creamy camembert to tangy cheddar. But how are they made?

Adam - The main ingredient for making cheese is milk and for most cheese this means cow’s milk.

Hannah - Although, goat, sheep and even buffalo milk are used too. The first stage of transforming liquid milk into cheese is called souring.

Adam - This is when bacteria - either those naturally found in raw milk or added to pasteurized milk - digest the lactose sugar present in milk and convert it to lactic acid, making the milk sour.

Hannah - This acidic environment helps with the next stage - coagulation - where moisture is squeezed out. Milk is clotted under the influence of an enzyme called chymosin - also known to cheesemakers as rennet.

Adam - Rennet causes proteins in the milk to clump together, which starts to separate out from the watery whey as solid curds.

Hannah - These curds are a 3-dimensional net of tiny, sticky proteins that trap fat globules and bacteria.

Adam - Once the curds have set they are cut into pieces and the water drained away…

Hannah - Depending on the exact process used - and there are a lot of potential combinations of time, temperature, cutting, stirring and pressing that can be inflicted on a vat of curd - the same milk can be transformed into all sorts of different cheeses.

Adam - The curds are mixed with salt, pressed into moulds and left to age and mature.

Hannah - As the cheese ages - the salt, moisture, temperature, acidity and nutrients available in the curds determine which microbes grow and thrive...

Adam - Microbial enzymes break down tasteless fats and proteins into small volatile molecules creating the tastes and smells of the cheeses we love…

Chris - Don't we just! Thank you to Hannah and Adam for that. And now with us to taste our way through the microbiology of cheese is Bronwen Percival, she's the cheese buyer at Neal's Yard Dairy in London. She's also the co-author of the book Reinventing the Wheel - milk, microbes and the fight for real cheese. And very pleased to say she has what looks like a delicious place of cheese in front of her. What have you brought in?

Bronwen  - I have brought you two different goats cheeses from a farm in Staffordshire called Highfields farm dairy. And the thing that makes them really special is that they are made without added microbes, expressing just the microbial communities in that farm's milk, but actually doing it in two completely different ways.

Chris - So when you say just the microbes that are there, so you take the milk from the animal and the microbes that are naturally in that milk are then used to create the process that we've just heard about in order to produce these changes and these flavours?

Bronwen - That's correct. And if you look back about 120 years, nobody was adding microbes to the milk that they were using to make cheese.

Milk is sterile when it leaves the udder of a healthy animal but then it has many many opportunities to be inoculated with naturally occurring microbes from the environment and that could be from the udder, from the skin of the teat -

Chris - from the hands of the farmer?

Bronwen - Absolutely

There are a lot of interesting lactic acid bacteria, the bacteria that then ferment the milk turn the lactose into the lactic acid, that lies at the very centre of the cheese making process, but there are also lots of interesting ripening bacteria that are responsible for a lot of the flavour development as the cheese matures, and many of those ripening bacteria are actually skin bacteria.

Chris - So basically the environment where a lot of milk is collected, stored and cheese is made is gonna become overtime a complete bacterial banquet going on, there’s going to be loads of those microbes. And so a cheese making area is gonna become better as time goes on, there will be  a big enrichment for the right sorts of bacteria. And funghi.

Bronwen - Absolutely. And one of the really interesting things is looking at which microbes dominate in different areas of the farm and then how those manifest themselves on the outside or the inside of the cheese. And so the microbes that are dominating at Highfields farm dairy where these cheeses that we're tasting are from, they might be lactococcus lactis just like you could see at a different farm but chances are good that they’re different strains of the same species of microbe and that those are going to give those cheeses specific different flavors.

Chris - Now if you pasteurized milk does that not destroy all the microbes and would that mean that that milk would be useless for cheese making, you'd have to add microbes back in if you had pasteurized the milk?

Bronwen - So pasteurization is heat treating the milk so it takes out a wide variety of the microbes in the milk. It doesn't kill all of the microbes in the milk though. There are thermoduric bacteria that survive pasteurization and many of the ripening bacteria you find on the outside of certain washed rind cheeses for example are thermoduric  and can have come from the original raw milk.

So it's not to say that it wipes the microbial slate clean, but it definitely decreases the diversity of what's going on in there.

Chris - Well I'm being assailed with these lovely smells that are coming off this plate. Talk me through these two cheeses one of them is a much harder looking cheese and the other one is a round, sausage shaped piece of cheese, so what are the two? How do they differ?

Bronwen - So the hard cheese is a fairly new cheese it's called Highfields and Joe and Amy the cheese makers decided that they wanted to start making it because they were really interested as English cheesemakers in making a typically English style of cheese.

Chris - It's delicious. I’ll tell Joe right now. It's just lovely cheese. Excellent. Hang on Georgia says she wants some.

Georgia - Yes please!

Bronwen - British cheeses really like to have milk that's stored overnight at a fairly warm temperature to allow those native microbes to start multiplying and growing within the milk. We call this pre-ripening and it's very interesting that that is also a technique that's shared by the other style cheese on this plate which we also associate much more with farms in France. So those sausage seep cheese is called Innes Log, quite fresh, quite acidic a little bit of a funky rind, it looks a bit brainy on the outside, and so by taking the same raw material this milk and then putting it through two separate processes you're able to select for different sets of bacteria which then grow within those different substrates and create cheeses with utterly different flavours.

Chris - So basically you're selecting strongly selecting by varying the environments in which you make the cheese and the techniques you used to make the cheese, for slightly different populations of microbes. And it's that shift in microbial population that means that you get slightly different biochemistries, altering and what's the starting material but also adding their own particular flavor fingerprint.

Bronwen -  Exactly. So in just the same way as if you're setting out to make a batch of sauerkraut you need to provide a salty environment and you need to provide an anaerobic environment to select for those microbes.

Georgia - This might be a dumb question but Swiss cheese with all the holes in. Do microbes do that as well?

Bronwen -  They certainly do. The holes in Swiss cheese are caused by a bacterium called propionibacterium and they produce gas during the ripening process and you get those really beautiful round holes.

There are also other microbes that produce gas during the maturation process that can cause defects and sometimes you'll see those styles of cheeses, instead of having holes actually having great big chasms and cracks in the middle of them. And those are caused by clostridium bacteria which can produce hydrogen gas and also butyric acid  -

Chris - Smells like vomit!

Bronwen - It does, it’s the principle flavour component of vomit and you can imagine that the cheeses that have these microbes growing in them during their maturation, they taste like sick and they're completely unsellable not to mention that they have massive cracks in them!

Chris - One quick question that occurs me, talking about selection of bacteria. Why is there such a contrast between cheese that say a cow’s milk cheese and cheese which is say a goat's or sheep's milk cheese? You can tell what you're eating by the flavour profile. Is that because the starting composition of the milk is different or is it because the microbial spectrum is different or is it both?

Bronwen - I would say it's probably both. Cow’s milk has different fatty acid composition than goat's milk and sheep's milk and with goat's milk you can get these fatty acids caproic acid, caprylic acid all from capra which is goat, which have that really goaty taste. If you have really fresh goat's milk where the fats haven't yet started to break down it doesn't taste goaty at all, but the moment you start getting that breakdown you get really goaty flavors and so yes there is a lot to do with the initial composition of of the milk.

Chris - Are people sciencing the hell out of this food? In other words are people now using the power of microbiology and our understanding of biotechnology to spike the mixture with some magic microbes that could make even more exciting flavours, textures, types of cheese?

Bronwen - Yes people have been working to try to develop cultures of bacteria that will bring out specific flavours for years and years and there are already many of these designer cultures on the market.

At the same time it's a really exciting time for farmhouse cheesemakers because there are many scientists out there microbiologists who are looking for model systems to study microbial community formation and they've found that actually unlike the gut microbiota which need very very anaerobic conditions that are difficult to maintain in a laboratory, cheese is a system which all you need is a wine cooler and you can grow your own cheese rinds and look at them in great detail, and start to use them to tease apart some of these basic principles of microbial competition, communication and so on.

Hand Washing

53:45 - QotW: Why won't old soap make suds?

When a bar of soap gets used a lot and gets smaller, it seems to struggle to form suds properly. Is something other than just a smaller surface area going on?

QotW: Why won't old soap make suds?

Eva has been scrubbing up to answer this question from William...

Eva - Alan Calverd from the forum said "my guess is that most soaps include volatile and easily soluble components that aid lathering, as the bar shrinks its surface to volume ratio increases. So these components are lost more rapidly". But what do the experts think. Phillip Broadwith, business editor at chemistry world for the Royal Society of Chemistry, gave us this answer.

Phillip - The reason a small soap bar doesn't make such a good lather is mostly down to surface area. To form bubbles you need to dissolve soap in water and then agitate it and with a small bar of soap you can only dissolve the soap molecules at the surface of the bar. With a large bar the water on your wet hands is in contact with quite a large area, so can dissolve quite a lot of soap quite quickly and make a generous lather. But with the smaller bar you surface area in contact with your hand is smaller. So even if you have the same amount of water on your hands the soap is released more slowly.

Eva- Paul Dauenhauer, associate professor of chemical engineering and material science at the University of Minnesota, and soap enthusiast, had this to add.

Paul - A three dimensional object like a bar of soap that shrinks half its original size actually only has one eighth of the original surface area. People are not scrubbing with the bar that much longer and the perception is that they are not getting as much soap transferred to their hands.

Eva - Right. So by that math to use a bar of soap that's gone down to half its original size you'd need to be scrubbing your hands for eight times longer. No wonder we get impatient.

Paul - A second impact is a perception of the bar by the hand washer with time, soap bars are made of heavy molecules such as soap molecules but they also contain light components that enhance the handwashing experience. A person washing their hands is aware of some of the compounds that add color and odor but other components are added to have additional benefits such as stabilizing a foam or eliminating the effects of hard water.

Eva - Hard water, like we suffer in Cambridge, contains metals which bind to the soap molecules and stop them from being able to clean properly. Soap manufacturers add special compounds called chelants which will bind to the metals and protect the soap molecules. But what does this have to do with getting a good lather from a small bar of soap.

Paul - Overtime these lighter compounds will evaporate into the air or preferentially leach into the water faster than the heavier soap compounds. The end result is that the smaller soap bar is less effective later in its life at forming stable lathery foams that are good for washing your hands.

Eva - And Philip has an extra tip for the frustrated hand washes out there.

Phillip - You might be able to get a better lather by carefully adding more water to your hands. But that's quite difficult to do without washing off the existing lather. Alternatively when the bar is small enough try rubbing it over the backs of your wet hands as well as just the palms so it's exposed to more water to dissolve more soap.

Eva - So there you have it, next time we'll be answering this question from Marcus.

Marcus - How can oak trees and others grow so huge without making a great whole in the earth? Where does their mass come from if not from the dirt?Eva - Alan Calvert from the forum said my guess is that most soaps include volatile and easily soluble components that aid lathering, as the bar shrinks its surface to volume ratio increases. So these components are lost more rapidly. But what do the experts think. Phillip Broadwith, business editor at chemistry world for the Royal Society of Chemistry, gave us this answer.

Phillip - The reason a small soap bar doesn't make such a good lather is mostly down to surface area. To form bubbles you need to dissolve soap in water and then agitate it and with a small bar of soap you can only dissolve the soap molecules at the surface of the bar. With a large bar the water on your wet hands is in contact with quite a large area, so can dissolve quite a lot of soap quite quickly and make a generous lather. But with the smaller bar you surface area in contact with your hand is smaller. So even if you have the same amount of water on your hands the soap is released more slowly.

Eva- Paul Dauenhauer, associate professor of chemical engineering and material science at the University of Minnesota, and soap enthusiast, had this to add.

Paul - A three dimensional object like a bar of soap that shrinks half its original size actually only has one eighth of the original surface area. People are not scrubbing with the bar that much longer and the perception is that they are not getting as much soap transferred to their hands.

Eva - Right. So by that math to use a bar of soap that's gone down to half its original size you'd need to be scrubbing your hands for eight times longer. No wonder we get impatient.

Paul - A second impact is a perception of the bar by the hand washer with time, soap bars are made of heavy molecules such as soap molecules but they also contain light components that enhance the handwashing experience. A person washing their hands is aware of some of the compounds that add color and odor but other components are added to have additional benefits such as stabilizing a foam or eliminating the effects of hard water.

Eva - Hard water, like we suffer in Cambridge, contains metals which bind to the soap molecules and stop them from being able to clean properly. Soap manufacturers add special compounds called chelants which will bind to the metals and protect the soap molecules. But what does this have to do with getting a good lather from a small bar of soap.

Paul - Overtime these lighter compounds will evaporate into the air or preferentially leach into the water faster than the heavier soap compounds. The end result is that the smaller soap bar is less effective later in its life at forming stable lathery foams that are good for washing your hands.

Eva - And Philip has an extra tip for the frustrated hand washes out there.

Phillip - You might be able to get a better lather by carefully adding more water to your hands. But that's quite difficult to do without washing off the existing lather. Alternatively when the bar is small enough try rubbing it over the backs of your wet hands as well as just the palms so it's exposed to more water to dissolve more soap.

Eva - So there you have it, next time we'll be answering this question from Marcus.

Marcus - How can oak trees and others grow so huge without making a great whole in the earth? Where does their mass come from if not from the dirt?

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